Durlobactam, a Broad-Spectrum Serine ß-lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species

被引：23

作者：

Papp-Wallace, Krisztina M. ^{[1
,2
,4
]}

McLeod, Sarah M. ^{[3
]}

Miller, Alita A. ^{[3
,5
]}

机构：

[1] Vet Affairs Northeast Ohio Healthcare Syst, Res Serv, Cincinnati, OH USA

[2] Case Western Reserve Univ, Dept Biochem & Med, Cleveland, OH USA

[3] Entasis Therapeut, Waltham, MA USA

[4] Northeast Ohio Vet Healthcare Syst, 10701 East Blvd, Cleveland, OH 44106 USA

[5] Entasis Therapeut, 35 Gatehouse Dr, Waltham, MA 02451 USA

来源：

CLINICAL INFECTIOUS DISEASES | 2023年 / 76卷

关键词：

Acinetobacter; sulbactam; durlobactam; beta-lactamase inhibitor; diazabicyclooctane; IN-VITRO ACTIVITY; BETA-LACTAMASE; ANTIMICROBIAL ACTIVITY; IMIPENEM-RESISTANT; BAUMANNII; SULBACTAM/DURLOBACTAM; REVERSIBILITY; COMBINATION; INFECTIONS; HOSPITALS;

D O I：

10.1093/cid/ciad095

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Sulbactam-durlobactam is a pathogen-targeted ss-lactam/ss-lactamase inhibitor combination in late-stage development for the treatment of Acinetobacter infections, including those caused by multidrug-resistant strains. Durlobactam is a member of the diazabicyclooctane class of ss-lactamase inhibitors with broad-spectrum serine ss-lactamase activity. Sulbactam is a first-generation, narrow-spectrum ss-lactamase inhibitor that also has intrinsic antibacterial activity against Acinetobacter spp. due to its ability to inhibit penicillin-binding proteins 1 and 3. The clinical utility of sulbactam for the treatment of contemporary Acinetobacter infections has been eroded over the last decades due to its susceptibility to cleavage by numerous ss-lactamases present in this species. However, when combined with durlobactam, the activity of sulbactam is restored against this problematic pathogen. The following summary describes what is known about the molecular drivers of activity and resistance as well as results from surveillance and in vivo efficacy studies for this novel combination.

引用

页码：S194 / S201

页数：8

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